The Role of Dysregulated miRNAs in the Pathogenesis, Diagnosis and Treatment of Age-Related Macular Degeneration

Abstract

Age-related macular degeneration (AMD) is an eye disease causing damage to the macular region of the retina where most of the photoreceptors responsible for central visual acuity are located. MicroRNAs (miRNAs) are small single-stranded non-coding RNA molecules that negatively regulate genes by silent post-transcriptional gene expressions. Previous studies have shown that changes in specific miRNAs are involved in the pathogenesis of eye diseases, including AMD. Altered expressions of miRNAs are related to disturbances of regulating oxidative stress, inflammation, angiogenesis, apoptosis and phagocytosis, which are known factors in the pathogenesis of AMD. Moreover, dysregulation of miRNA is involved in drusen formation. Thus, miRNAs may be used as potential molecular biomarkers for the disease and, furthermore, tailoring therapeutics to particular disturbances in miRNAs may, in the future, offer hope to prevent irreversible vision loss. In this review, we clarify the current state of knowledge about the influence of miRNA on the pathogenesis, diagnosis and treatment of AMD. Our study material consisted of publications, which were found in PubMed, Google Scholar and Embase databases using “Age-related macular degeneration”, “miRNA”, “AMD biomarkers”, “miRNA therapeutics” and “AMD pathogenesis” as keywords. Paper search was limited to articles published from 2011 to date. In the section “Retinal, circulating and vitreous body miRNAs found in human studies”, we limited the search to studies with patients published in 2016–2021.

The regulatory role of microRNAs in common eye diseases: A brief review

“…Studies revealed that circulating miRNAs could also serve as potential biomarkers for AMD detection (Urbańska et al, 2022;Elshelmani and Rani, 2023), as reported in other chronic diseases, such as cancer (El-Daly et al, 2023), osteoporosis (Messner et al, 2022), epilepsy (Xie et al, 2023), pulmonary hypertension (Düzgün et al, 2023), nephropathies (Sun et al, 2022), and hepatitis (Jiang et al, 2023). Furthermore, the significance of circulating miRNAs in numerous therapeutic areas makes them a promising asset for translational medicine applications (Pozniak et al, 2022).…”

Decoding the secrets of longevity: unraveling nutraceutical and miRNA-Mediated aging pathways and therapeutic strategies

“…Treatment targets for AMD are thought to include several miRNAs implicated in either retinal pigment epithelium atrophy or choroidal neovascularization ( Urbańska et al, 2022 ). For neovascular AMD, anti-vascular endothelial growth factor therapy is a crucial treatment ( Cornel et al, 2015 ).…”

“…The miR-15/107 group, the miR-17∼92 cluster, miR-21, miR-132, miR-296, miR-378, and miR-519c are some of these miRNAs. It is thought that miR-23a mimics reduce macular related-apoptosis whereas miR-23a inhibition increases it ( Ren et al, 2017 ; Urbańska et al, 2022 ).…”

Antioxidative Role of Heterophagy, Autophagy, and Mitophagy in the Retina and Their Association with the Age-Related Macular Degeneration (AMD) Etiopathogenesis

“…Their disruption or malfunction leads to many general disorders (cancer, inflammation, diabetes, cardiovascular, and neurologic diseases) [153,154]. Altered expressions (dysregulations) of different miRNAs are involved in AMD etiopathogenesis [155][156][157]. Circulating miRNAs may be potential diagnostic biomarkers for AMD [158,159].…”

“…According to another study, miRNA-23, miRNA-27a, miRNA-34, miRNA-126, miRNA-146a, and miRNA-155 are the most frequently dysregulated miRNAs in AMD. All of them are associated with oxidative stress, apoptosis, inflammation, and angiogenesis; however, in oxidative stress, miRNA-27a and miRNA-146a are mainly involved; miRNA-27a affects RPE by prooxidants, and miRNA-146a is up-regulated by ROS [155].…”